Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair (original) (raw)

• Letter
• Published: 01 April 2012
• Katsuyoshi Horibata1,2 na1,
• Masafumi Saijo1 na1,
• Chie Ishigami1,
• Akiko Ukai2,
• Shin-ichiro Kanno3,
• Hidetoshi Tahara4,
• Edward G Neilan5,
• Masamitsu Honma2,
• Takehiko Nohmi2,
• Akira Yasui3 &
• …
• Kiyoji Tanaka1

Nature Genetics volume 44, pages 593–597 (2012)Cite this article

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Abstract

UV-sensitive syndrome (UVSS) is an autosomal recessive disorder characterized by photosensitivity and deficiency in transcription-coupled repair (TCR), a subpathway of nucleotide-excision repair that rapidly removes transcription-blocking DNA damage1. Cockayne syndrome is a related disorder with defective TCR and consists of two complementation groups, Cockayne syndrome (CS)-A and CS-B, which are caused by mutations in ERCC8 (CSA) and ERCC6 (CSB), respectively2. UVSS comprises three groups, UVSS/CS-A, UVSS/CS-B and UVSS-A, caused by mutations in ERCC8, ERCC6 and an unidentified gene, respectively3,4,5,6. Here, we report the cloning of the gene mutated in UVSS-A by microcell-mediated chromosome transfer. The predicted human gene UVSSA (formerly known as KIAA1530)7 corrects defective TCR in UVSS-A cells. We identify three nonsense and frameshift UVSSA mutations in individuals with UVSS-A, indicating that UVSSA is the causative gene for this syndrome. The UVSSA protein forms a complex with USP7 (ref. 8), stabilizes ERCC6 and restores the hypophosphorylated form of RNA polymerase II after UV irradiation.

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Acknowledgements

We thank Y. Iwamoto and I. Kuraoka for their help in DNA sequencing and microcell-mediated chromosome transfer and M. Hoshi for her help in establishing Flp-In cells and performing immunoprecipitation. We also thank M. Yamaizumi (Kumamoto University Medical School) and N.G. Jaspers (Erasmus Medical Centre) for providing Kps3 cells and TA-24 cells, respectively. We thank G. Spivak for critical reading of the manuscript. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and by Health and Labor Sciences Research Grants for Research on Intractable Diseases (to K.T.). Part of this work was carried out under the Cooperative Research Project Program of the Institute of Development, Aging and Cancer (IDAC) at Tohoku University.

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1. Xue Zhang, Katsuyoshi Horibata and Masafumi Saijo: These authors contributed equally to this work.

Authors and Affiliations

1. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
   Xue Zhang, Katsuyoshi Horibata, Masafumi Saijo, Chie Ishigami & Kiyoji Tanaka
2. Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo, Japan
   Katsuyoshi Horibata, Akiko Ukai, Masamitsu Honma & Takehiko Nohmi
3. Division of Dynamic Proteome, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
   Shin-ichiro Kanno & Akira Yasui
4. Department of Cellular and Molecular Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
   Hidetoshi Tahara
5. Division of Genetics, Children's Hospital Boston, Center for Life Science Boston, Boston, Massachusetts, USA
   Edward G Neilan

Authors

1. Xue Zhang
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2. Katsuyoshi Horibata
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3. Masafumi Saijo
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4. Chie Ishigami
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5. Akiko Ukai
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6. Shin-ichiro Kanno
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7. Hidetoshi Tahara
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8. Edward G Neilan
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9. Masamitsu Honma
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10. Takehiko Nohmi
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11. Akira Yasui
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12. Kiyoji Tanaka
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Contributions

X.Z., K.H., M.S. and K.T. conceived the experiments. K.T. and H.T. established the cell lines. X.Z., K.H. and C.I. performed microcell-mediated chromosome transfer. A.U., K.H. and M.H. performed CGH array analysis. X.Z., M.S. and S.K. performed biochemical analysis. E.G.N. diagnosed Cockayne syndrome patients. K.T., X.Z., K.H., M.S., M.H., T.N. and A.Y. analyzed the data. K.T., X.Z., M.S. and K.H. wrote the manuscript.

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Correspondence toKiyoji Tanaka.

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Zhang, X., Horibata, K., Saijo, M. et al. Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair.Nat Genet 44, 593–597 (2012). https://doi.org/10.1038/ng.2228

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• Received: 26 September 2011
• Accepted: 29 February 2012
• Published: 01 April 2012
• Issue Date: May 2012
• DOI: https://doi.org/10.1038/ng.2228

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